Microphthalmia in Texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (PITX3) gene

Becker, Doreen; Tetens, J.; Brunner, A.; Burstel, D.; Ganter, M.; Kijas, J.; Drögemüller, Cord (2010). Microphthalmia in Texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (PITX3) gene. PLoS ONE, 5(1), e8689. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0008689

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Microphthalmia in sheep is an autosomal recessive inherited congenital anomaly found within the Texel breed. It is characterized by extremely small or absent eyes and affected lambs are absolutely blind. For the first time, we use a genome-wide ovine SNP array for positional cloning of a Mendelian trait in sheep. Genotyping 23 cases and 23 controls using Illumina's OvineSNP50 BeadChip allowed us to localize the causative mutation for microphthalmia to a 2.4 Mb interval on sheep chromosome 22 by association and homozygosity mapping. The PITX3 gene is located within this interval and encodes a homeodomain-containing transcription factor involved in vertebrate lens formation. An abnormal development of the lens vesicle was shown to be the primary event in ovine microphthalmia. Therefore, we considered PITX3 a positional and functional candidate gene. An ovine BAC clone was sequenced, and after full-length cDNA cloning the PITX3 gene was annotated. Here we show that the ovine microphthalmia phenotype is perfectly associated with a missense mutation (c.338G>C, p.R113P) in the evolutionary conserved homeodomain of PITX3. Selection against this candidate causative mutation can now be used to eliminate microphthalmia from Texel sheep in production systems. Furthermore, the identification of a naturally occurring PITX3 mutation offers the opportunity to use the Texel as a genetically characterized large animal model for human microphthalmia.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics

UniBE Contributor:

Becker, Doreen and Drögemüller, Cord

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:32

Last Modified:

07 Aug 2015 04:03

Publisher DOI:

10.1371/journal.pone.0008689

Web of Science ID:

000273554600037

BORIS DOI:

10.7892/boris.12506

URI:

https://boris.unibe.ch/id/eprint/12506 (FactScience: 218860)

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